Indole regulation of antigen presenting cells

Abstract

The disclosure provides methods and compositions for affecting the development of antigen presenting cell (APC, e.g., a macrophage or dendritic cell). The methods include maturing an APC, promoting anti-inflammatory phenotype, promoting development of a T regulatory cell (Treg) from a naive T cell. The methods generally include exposing an APC to a tryptophan derived microbiota metabolite (TDMM), such as an anti-inflammatory or pro-mucosal TDMM, and permitting the APC to mature. In some embodiments, the conditioned APC is exposed to a naive T cell to further promote development of a T regulatory cell (Treg). In some embodiments, the TDMM is selected from the group consisting of indole, indole-3-acetate, 5-hydroxyindole, and indole-3-pyruvate.

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows: 
     
       1. A method of maturing an antigen presenting cell (APC), comprising contacting an immature APC in vitro with an effective amount of a composition comprising isolated or purified indole, and permitting maturation of the APC. 
     
     
       2. The method of  claim 1 , wherein the APC is a dendritic cell. 
     
     
       3. The method of  claim 2 , wherein the APC is a gut-associated lymphoid tissue (GALT) dendritic cell. 
     
     
       4. The method of  claim 1 , wherein the APC is a macrophage. 
     
     
       5. The method of  claim 1 , further comprising exposing the immature APC to an antigen to which tolerance is desired. 
     
     
       6. The method of  claim 1 , wherein the mature APC exhibits an anti-inflammatory phenotype. 
     
     
       7. The method of  claim 1 , further comprising exposing the mature APC to a naïve T cell in vivo or ex vivo. 
     
     
       8. A method of promoting anti-inflammatory phenotype, comprising contacting an immature antigen presenting cell (APC) in vitro with a composition comprising isolated or purified indole. 
     
     
       9. The method of  claim 8 , wherein promoting anti-inflammatory phenotype comprises promoting peripheral tolerance of antigens in the gut of a subject. 
     
     
       10. The method of  claim 8 , wherein the APC is a dendritic cell. 
     
     
       11. The method of  claim 10 , wherein the APC is a mucosal dendritic cell. 
     
     
       12. The method of  claim 10 , wherein the APC is a gut-associated lymphoid tissue (GALT) dendritic cell. 
     
     
       13. The method of  claim 8 , wherein the APC is a macrophage. 
     
     
       14. The method of  claim 8 , further comprising administering the exposed APC to the subject. 
     
     
       15. The method of  claim 8 , further comprising exposing the mature APC to a naïve T cell in vivo. 
     
     
       16. A method of promoting development of a T regulatory cell (Treg) from a naive T cell, comprising contacting the naive T cell to an antigen presenting cell (APC) that has been conditioned in vitro or ex vivo with a composition comprising isolated or purified indole. 
     
     
       17. The method of  claim 16 , wherein the Treg has an increased FoxP3 expression as compared to the naïve T cell. 
     
     
       18. The method of  claim 16 , wherein the indole-conditioned APC is produced by contacting an immature APC to the composition comprising the isolated or purified indole and permitted to mature. 
     
     
       19. The method of  claim 18 , wherein the APC is a dendritic cell or macrophage. 
     
     
       20. The method of  claim 19 , wherein the dendritic cell is a gut-associated lymphoid tissue (GALT) dendritic cell. 
     
     
       21. The method of  claim 16 , wherein the Treg is produced in vitro and is administered to a subject in need.